Scripps Research-led study may improve HIV, flu vaccines

This graphic shows how the computer-designed protein, in red, binds to a broadly neutralizing antibody against HIV called VRC01, in magenta and yellow. A team led by scientists at The Scripps Research Institute designed the protein to stimulate the immune system to make the antibody.

This graphic shows how the computer-designed protein, in red, binds to a broadly neutralizing antibody against HIV called VRC01, in magenta and yellow. A team led by scientists at The Scripps Research Institute designed the protein to stimulate the immune system to make the antibody.

LA JOLLA -- More effective vaccines against fast-mutating viruses like HIV and influenza may be possible with a new model from a team led by scientists from The Scripps Research Institute.

The computer-designed model stacks virus-derived proteins in an array like a real virus. In lab cultures, the virus-like particles activated immune cells that make broadly neutralizing antibodies.

The scientists plan to try this approach in rodents. Human clinical trials may follow.

The study was published Thursday in an online edition of the journal Science. William R. Schief of Scripps led the study. Its first author was Joseph Jardine, a student of Schief’s.

Broadly neutralizing antibodies attack many viral strains, making it harder for viruses to evolve resistance. Some asymptomatic HIV-infected people produce them. Ian Wilson, head of the International Aids Vaccine Initiative'sNeutralizing Antibody Center at Scripps, and Scripps colleague Dennis Burton have been collecting them for years. Both are study co-authors. Burton heads an HIV vaccine center at Scripps created last year with a $77 million grant from the National Institutes of Health.

With the antibodies in hand, researchers are trying to "reverse-engineer ", as the study authors put it, how these antibodies are made to make a vaccine to teach the immune system to make them.

One class of broadly neutralizing antibodies, called VRCO1, hold special promise, because they can neutralize 90 percent of known HIV strains. They are made by certain immune system cells called B cells. Less mature B cells, called "germline" cells, are responsible for eliciting long-term immunity, so they are especially important.

However, the most obvious target proteins, those that envelope HIV, don't bind well to these B cells. So the scientists performed computer modeling to produce modified HIV proteins that would bind tightly to these antibodies and so trigger an immune response from the B cells. With help from the IAVI center, Schieff’s team arrived at the best candidate immunogen, which they named eOD-GT6.

“We wanted to know whether eOD-GT6 looked the way we anticipated and whether it bound to the antibody in the way that we predicted—and in both cases the answer was ‘yes’,” Jean-Philippe Julien, a senior research associate in the Wilson laboratory, said in a Scripps statement on the study. “We also were able to identify the key mutations that conferred its reactivity with germline VRC01 antibodies.”

The team coated copies of the protein onto bacterial enzymes to make the virus-like particles.

“We’re hoping that this approach can be used not just for an HIV vaccine, but for many other vaccines, too,” said Sergey Menis, a Scripps scientist and study author, in the statement.

However, the scientists wrote in the study that their work didn't explain how the immune systems of HIV-positive people with broadly neutralizing antibodies produced them in the first place.